Distribution of human CMV-specific memory T cells among the CD8(pos.) subsets defined by CD57, CD27, and CD45 isoforms

Chronic antigenic stimulation has been associated with peripheral blood expansions of CD(pos.) T cells characterized by CD57 expression, loss of CD27 expression, and reversal of the CD45RO(bright)/RA(dim) phenotype usually associated with immunological memory towards a CD45RO(dim)/RA(bright) phenotype. However, the relationship and functional significance of these subset(s) has remained controversial. Here, this issue was addressed using a novel flow cytometric technique that allows simultaneous detection of human cytomegalovirus (HCMV)-specific CD8(pos.) memory T cells by rapid (< 6 h) HCMV peptide-specific induction of cytokine synthesis, and their phenotypic characterization, including CD57, CD27 and CD45RA/RO. The vast majority of resting CD8(pos.) T cells capable of rapid induction of IFN-γ and TNF-α synthesis in response to HCMV peptides were found in a subset characterized by intermediate to high expression of CD57, down-regulation/loss of CD27, and varying degrees of reversal of the classical 'memory' CD45RO(bright)/RA(dim) phenotype. This subpopulation likely includes the fully differentiated memory cells responsible for the long-term immune defense against HCMV reactivation.